Neurology - Neurological infections

Question 1

How do bacteria gain access to the CNS?

Answer 1

CNS is normally sterile - 3 routes:

1) Direct spread from adjacent focus of infection - e.g. paranasal sinus, middle ear, or open skull fracture
2) Blood borne spread as a consequence of septicaemia or from a septic emboli elsewhere e.g. bacterial endocarditis or bronchiectasis
3) Iatrogenic infection - introduction of organisms following an LP. Low grade meningitis can occur in 20% of patients with a ventricular shunt (skin commensals)

Question 2

What is pachymeningitis?

Answer 2

Meningitis as a clinical term usually means inflammation within the subarachnoid space involving the arachnoid and pia mater

Pachymeningitis = inflammation predominantly involving the dura mater

Question 3

What causes pachymeningitis?

Answer 3

Usually caused by direct spread from an adjacent focus of infection from the bones of the skull following otitis media or mastoiditis

Specific organisms include:

• Gram negative bacilli from middle ear
• Alpha or beta haemolytic strep from paranasal sinuses
• Mixed organisms from skull fracture

An epidural or subdural abscess usually results

Question 4

Epidural abscess

Answer 4

Caused by suppuration between the dura mater and the skull or vertebral column

Act as a SOL and require drainage

Question 5

Subdural abscess

Answer 5

This is an uncommon lesion because pus can readily spread within the subdural space to form a subdural empyema

If subdural vessels are involved then cerebral cortical thrombophlebitis with infarction can occur

Question 6

Leptomeningitis

Answer 6

This is “classic” meningitis caused by inflammation in the subarachnoid space between the arachnoid and pia

Question 7

What causative organisms most commonly cause bacterial meningitis in neonates?

Answer 7

Group B strep (e.g. strep agalectiae) is most common followed by

• E. coli
• Listeria

Risk is increased in:

• Prematurity
• Prolonged membrane rupture
• Traumatic delivery
• Congenital malformations

NB - Listeria can also affect susceptible individuals (e.g. pregnant women, alcoholics, immunocompromised etc), rapidly progressing picture resembling brainstem encephalitis + focal signs + meningism, treat with ampicillin

Question 8

What is the most common cause of bacterial meningitis in 3 months - 3 year age group?

Answer 8

H. influenza type B related to nasopharyngeal colonisation

Question 9

In which age group is Neisseria meningitis most common?

Answer 9

Children and young adults

Nasopharyngeal colonisation leads to haematogenous dissemination and meningitis, occurring in epidemics

Low complement increases risk

Question 10

In what group is S. pneumoniae causative for bacterial meningitis?

Answer 10

Elderly and alcoholics (also consider Klebsiella) - increased with age dependent reduction in immunity

Also post traumatic as S.pneumoniae part of normal flora of URT - increased risk with cerebrospinal fluid fistula

Question 11

What agents are post neurosurgical patients at risk of for bacterial meningitis?

Answer 11

• Staph epidermidis
• Staph aureus
• Enterobacteriaecae
• Pseudomonas
• Pneumococci

Question 12

Pathology of bacterial meningitis - what structures can be damaged/ involved?

Answer 12

Blood brain barrier limits host defences

Bacteria in CSF trigger inflammatory reaction in vascular pia - causes exudate of blood proteins and PML migration

Thrombosis of superficial veins causes brain infarction

Accumulation of exudate can obstruct CSF (especially in the basal cisterns where it can obstruct the 4th ventricle exit foramina)

Penetration of the arachnoid causes subdural inflammation and effusions

Structures in the subarachnoid space such as the cranial nerves can become damaged; deafness (damage to VIIIth CN in the basal cisterns) is a common complication of meningitis in children

Retrograde spread from CSF into ventricles can cause centriculitis

Question 13

Symptoms of bacterial meningitis

Answer 13

The classic triad is fever, neck stiffness and headache

Patients may have a prodrome phase

• Resp infection or otitis media
• Associated muscle pain (myalgia)

Other symptoms include coma, drowsiness, vomiting, generalised seizures

Question 14

Signs of meningitis

Answer 14

Signs of meningeal irritation:
- Neck stiffness on forward flexion, inability to completely extend legs (Kerning’s sign)

Bulging of anterior fontanelles in neonates/ infants

Petechial and purpuric rash with circulatory collapse - characteristic of Waterhouse-Friderichsen syndrome in meningococcal disease

Look for sepsis elsewhere:

• Ears
• URT
• Lung
• Heart valves
• CSF leak (post traumatic and post surgical patients)

Question 15

What are the lumbar puncture findings in bacterial meningitis?

Answer 15

LP is THE investigation of choice to confirm meningitis

• Raised opening pressure (20-40mm H2O)
• Cloudy/ turbid
• PML pleocytosis
• Elevated protein
• low glucose (under 40% that of simultaneously measured blood glucose)

Bacteria may be visible under gram stain
PCR can be used to detect bacterial antigens in partially treated meningitis

Question 16

Other investigations in meningitis?

Answer 16

• Increased WCC with left shift
• Blood and throat cultures: source of infection and evidence of systemic sepsis
• Imaging: CT/ MRI to exclude principle differentials for meningitis (subdural empyema, brain abscess and encephalitis)

Question 17

Can an LP be performed without a prior CT scan?

Answer 17

LP must be preceded by a CT (or MRI) if there is any evidence of impaired of consciousness, focal neurology, or prior seizure due to the risk of tonsillar herniation or coning

Question 18

Meningitis is a neurological emergency. What antibiotics are used to treat neonatal bacterial meningitis?

Answer 18

Either:

• Ampicillin + Third generation cephalosporin, or
• Ampicillin + gentamicin

(Remember 3rd gen cephalosporins have “t” or “tri” in their name)

Question 19

Antibiotics used to treat bacterial meningitis in older children and adults

Answer 19

Ceftriaxone or cefotaxime + ampicillin (if Listeria suspected)

Question 20

What antibiotics are used in patients over 50 or alcoholics with bacterial meningitis?

Answer 20

Third generation cephalosporin (e.g. ceftriaxone) + IV vancomycin

Question 21

Should you wait for CSF microbiology to come back before starting antibiotics if you suspect meningitis?

Answer 21

Meningitis is a medical emergency requiring urgent antibiotics. These should be commenced as soon as possible when the disease is suspected, preferably after the CSF sample has been taken provided it does not interfere with treatment

Question 22

Complications of meningitis

Answer 22

• Cerebral infarction
• Obstructive hydrocephalus
• Cerebral abscess
• Subdural empyema
• Epilepsy

Question 23

What is the prognosis of meningitis?

Answer 23

Neonatal meningitis carries a mortality rate of 50% - of the survivors, 50% have permanent sequelae

S. pneumoniae meningitis - 25%

N. meningitidis - 10%

Question 24

How is the CNS affected by tuberculosis?

Answer 24

CNS tuberculosis is always secondary to infection elsewhere, usually the lungs

CNS involvement takes 2 forms:

(i) Tuberculous meningitis
(ii) Tuberculomas

Question 25

What causes TB meningitis?

Answer 25

Usually results from haematogenous spread from a primary (children and adults) or secondary complex (adults) in the lungs Rarely, it can result from direct spread of infection from a vertebral body to the meninges

Question 26

Characteristics of tuberculous meningitis

Answer 26

Thick gelatinous exudate which is most marked around the basal cisterns (basal meninges are worst affected) and within cerebral sulci On microscopy meningeal involvement consists of granulomas with central caseation and giant cells

Question 27

CSF findings of tuberculous meningitis

Answer 27

- Increased polymorphs initially then lymphocytes - Increased protein - Decreased or absent glucose - Clear or opalescent with fibrin webs Acid fast bacilli present on MC&S

Question 28

What are the clinical features of tuberculous meningitis?

Answer 28

Majority of patients are adults, TBM is rare in children now - Stage 1: non specific symptoms, fever, malaise - Stage 2: Confusion, isolated CN palsies, meningism, vasculitis (causing focal neurology - e.g. hemiparesis, ataxia, dysarthria) - Stage 3: coma

Question 29

What is a tuberculoma?

Answer 29

These are focal areas of granulomatous inflammation with caseation surrounded by a dense fibrous capsule Tuberculoma's usually present with symptoms of raised intracranial pressure - features of meningitis rarely occur

Question 30

Treatment for tuberculous meningitis

Answer 30

2 months of: - Rifampicin - Isoniazid - Pyrazinamide - Ethambutol 4 months of: - Rifampicin - Isoniazid

Question 31

What is Pott's disease?

Answer 31

This is chronic epidural infection following tuberculous osteomyelitis of the vertebral bodies Normally arises in the lower thoracic vertebra but can spread to several segments and may spread via the intervertebral foramina into the pleura, peritoneum or psoas muscle (causing a abscess)

Question 32

What is tuberculous meningomyelitis?

Answer 32

Inflammation of the leptomeninges (arachnoid and pia) results in an exudate that encases the spinal cord and nerve roots Patients present with back pain, paraesthesia, lower limb weakness and loss of bladder and bowel function This disorder is more common in AIDs patients

Question 33

What are spirochetes and which ones cause meningitis?

Answer 33

= Gram negative spiral shaped bacteria 1) Syphilis - treponema pallidum 2) Lyme disease - borrelia 3) Leptospirosis - leptospira

Question 34

Manifestations of neurosyphilis

Answer 34

Occurs in about 8% of untreated cases - 5 common presentations: 1) Asymptomatic neurosyphilis 2) Subacute meningitis (CSF shows high lymphocyte count) 3) Meningovascular syphilis 4) Tabes dorsalis (dorsal column and posterior root damage) 5) General paresis of the insane

Question 35

Lyme disease

Answer 35

Disease caused by Borrelia - transmitted by tick bites Characterised by: - Relapsing remitting arthralgia - Characteristic skin rash (erythema chronicum migrans) - Neurological features

Question 36

What are the clinical features of Lyme disease?

Answer 36

Only a minority of patients who get bitten by an infected tick develop the disease 3 stages: - Stage 1 - tick bite leads to arthralgia, flu like symptoms and a rash, antibiotics are usually curative - Stage 2 - several weeks/ months later; lymphocytic meningoencephalitis with facial nerve palsy + peripheral neuropathy - Stage 3 - several months/ years later: arthritis + diffuse CNS involvement with focal brain disease Treatment is with IV penicillin G

Question 37

What is leptospirosis?

Answer 37

Spirochete infection caused by leptospira species Transmitted by infected urine of domestic animals Only 10% of patients develop jaundice and haemorrhage complications (Weil's disease)

Question 38

Clinical features of leptospirosis

Answer 38

Incubation period for 10-12 days Then leptospiraemia (5-7 days): pyrexia, myalgia, rigors, hepatosplenomegaly, lymphadenopathy Followed by immune phase (variable duration): lymphocytic meningitis, cranial nerve palsies, encephalitis and (in Weil's disease) hepatic and renal failure

Question 39

What parasites infect the CNS?

Answer 39

Parasitic infection of the CNS is rare except in countries where human parasites are endemic Several cause neurological infection but 2 important ones are: i) Toxoplasma gondii - toxoplasmosis ii) Plasmodium falciparum - one form of malaria

Question 40

How is toxoplasmosis transmitted?

Answer 40

Eating uncooked meat or contact with faeces of an infected dog or cat

Question 41

What are the 2 forms of toxoplasmosis?

Answer 41

1) Congenital = previously unaffected woman contracts the infection during pregnancy; transplacental spread results in foetal infection - Hydrocephalus - Aqueduct stenosis - Microcephaly 2)Acquired = symptomatic infection uncommon but may be associated with immunosuppression - e.g. AIDS

Question 42

How does malaria infect the CNS?

Answer 42

Plasmodium falciparum causes cerebral malaria Infected RBCs adhere to vascular endothelium and block the microcirculation Endothelial damage produces cerebral oedema Patients develop confusion, focal signs, convulsions and coma

Question 43

Fungal CNS infections

Answer 43

Rare | Most are consequences of haematogenous spread from the lungs or paranasal sinuses

Question 44

Do all fungal infections occur in immunocompromised patients?

Answer 44

No - most CNS fungal infections occur in the immunocompromised, by cryptococcus neoformans is capable of producing disease in healthy individuals Cryptococcal infection usually presents as a subacute meningitis with a mild inflammatory reaction

Question 45

Opportunistic fungal infections of the CNS

Answer 45

Candida albicans Aspergillus fumigatus Both are usually secondary to respiratory infection Both cause meningitis with haemorrhage due to vascular invasion and characteristically produce multiple cerebral abscesses

Question 46

What is a rare fungal infection of the CNS that typically affects uncontrolled diabetics?

Answer 46

Mucormycosis Produces granulomatous mass in the paranasal sinuses that extends through the skull and frontal lobes Vascular invasion may result in cerebral infarction

Question 47

What are the lumbar puncture findings of fungal meningitis?

Answer 47

Same as TB - High lymphocyte count (lymphocytosis) - High opening pressure - High protein - Low glucose

Question 48

What stain is used to identify cryptococcus in CSF?

Answer 48

India ink preparation | Confirmed by positive latex agglutination test for cryptococcal polysaccharide antigen

Question 49

Viral spread to the CNS

Answer 49

i) Haematogenous spread as part of systemic infection with viraemia, usually causing meningitis or encephalitis ii) Neural spread along peripheral sensory nerves by retrograde axonal transport - Certain viruses exhibit neurotropism = a tendency to spread specifically to the CNS from the initial site of infection - e.g. polio from the gut

Question 50

Clinical features of viral meningitis

Answer 50

Presents with prominent headache and less obvious signs of meningeal irritation than in bacterial infections The causative organism is identified (PCR, CSF or serology) only 50% of the time - often enterovirus Viral meningitis is usually less severe than bacterial

Question 51

Name some causes of viral meningitis

Answer 51

- Echovirus 7, 11 - Coxsackie B1-5 - Coxsackie A9 - Mumps NB - many childhood exanthemata such as measles and chickenpox may be accompanied by meningitic illness which are usually mild and rarely life threatening

Question 52

CSF features of viral meningitis

Answer 52

- Normal CSF opening pressure - Mildly elevated or normal protein - Lymphocytosis - Normal glucose

Question 53

What is encephalitis? What are the clinical features?

Answer 53

= Infection of the brain parenchyma itself (rare) Clinical features are fever (not universal), headache, and a diffuse (i.e. confusion, drowsiness up to coma) rather than focal disturbance of cerebral function Others include: seizures, wandering, behavioural change, and frank psychotic symptoms

Question 54

How is encephalitis diagnosed?

Answer 54

Combination of clinical features + lymphocytosis in CSF CSF findings in encephalitis: - CSF pressure raised or normal - Protein mildly elevated or normal - Lymphocytosis - Normal glucose

Question 55

What other investigations are supportive in encephalitis?

Answer 55

- Focal inflammation on MRI - Focal slow wave activity on EEG - Organism detection (PCR, serology, culture) NB - large number of viruses can cause encephalitis and there is marked geographical variation (e.g. Japanese B in Far East, and West Nile in the USA) so a travel history is vital Cause is only identified in 30% of cases

Question 56

Herpes simplex virus encephalitis

Answer 56

Most treatable cause of encephalitis, but: - Rare: causes 20% of viral encephalitis - Presents with a viral prodrome followed by behavioural changes with amnesia and sometimes dysphasia - Rapid evolution into coma may occur - EEG shows repetitive epileptic discharges in the temporal lobe - CT/MRI shows necrotising inflammation in the temporal lobe

Question 57

What is the treatment for HSV encephalitis?

Answer 57

Immediate high dose aciclovir Prognosis is poor and long term sequelae are common: - 10% die acutely - 10% are severally impaired (requiring institutionalisation) - 20% are left dependent - 60% recover but with neuropsychological deficits (most do not function at their premorbid levels)

Question 58

Key features and agents of temporal lobe encephalitis

Answer 58

Herpes simplex most common Dysphasia and memory loss Diagnose by CT scan, LP (and PCR of CSF) Treat early (

Question 59

Key features and agents of brainstem encephalitis

Answer 59

``` Can be bacterial (Listeria) or viral Ataxia, dysarthria, diplopia Cranial nerve palsies Diagnose with MRI, LP Treat with antibiotics (ampicillin if Listeria) ```

Question 60

Herpes zoster infection

Answer 60

Latent viral infection Caused by reactivation of latent varicella zoster virus within sensory ganglia in the CNS (infection established following chickenpox in childhood) Reactivation occurs during intercurrent infection or immunosuppression Acute inflammation of the sensory ganglion (usually thoracic dorsal route or trigeminal ganglion) causes pain and hyperalgesia along the nerve distribution followed by erythema and vesicle formation

Question 61

What is progressive multifocal leucoencephalopathy?

Answer 61

Rare infection caused by the JC papovirus Most cases occur in immunosuppressed patients - e.g. in AIDS Virus causes cytolytic infection of oligodendrocytes resulting in demyelination of the white matter - usually fatal

Question 62

What is subacute sclerosing pan encephalitis?

Answer 62

Uncommon disease affecting children aged 7-10 Progressive neurological deficit with dementia and myoclonus leading to death SSP is caused by measles virus that is usually acquired before the age of 1 - large numbers of measles virus inclusion bodies present in neurones

Question 63

What viruses can cause antenatal infections?

Answer 63

Fetal CNS can be damaged during the first trimester of pregnancy following maternal infection with: - Toxoplasmosis - Other (e.g. syphilis) - Rubella - Cytomegalovirus - Herpes simplex virus 2 Cytomegalovirus and Rubella cause necrotising encephalitis leading to developmental damage and microcephaly

Question 64

Pathology of HIV CNS infection

Answer 64

HIV infects microglial cells forming multinucleate giant cells (of macrophage/ monocyte lineage) 80% of AIDS patients have CNS pathology at the time of death: - Cerebral HIV infection (causing progressive dementia) - Multiple opportunistic infections (e.g. Toxoplasma) - Other viral infections - Primary cerebral lymphoma

Question 65

What is acute disseminated encephalomyelitis?

Answer 65

This is an infrequent complication of measles, mumps and rubella infections (may also occur following vaccination for small pox and rabies) Onset is very sudden, usually 5-14 days after initial infection caused by T cell mediated delayed hypersensitivity response to a protein component of myelin Acute haemorrhage leucoencephalitis is a more severe related disorder - immune complex deposition in cerebral vessel walls